Créativité dans les espaces de coworking : mythes et réalités

Les espaces de coworking (ECW) sont considérés comme des espaces créatifs. À partir d’une étude qualitative auprès de gestionnaires et d’usagers d’ECW de la région de Montréal, nous avons exploré comment les mythes qui entourent la promesse de créativité se confrontent à la réalité et façonnent les pratiques des acteurs. Les résultats suggèrent des pratiques de compensation différenciées en regard de l’écart mythe-réalité : pratiques de revalorisation pour les gestionnaires et pratiques de développement d’un entre-soi pour les usagers.Coworking spaces (ECW) are considered creative spaces. Based on a qualitative study of ECW managers and coworkers in the Montreal area, we explored how the myths that pertain to creativity confront reality and shape the practices of actors. The results suggest differentiated compensatory practices with respect to the myth-reality gap: practices of revalorization for managers and practices of “entre-soi” for coworkers.Los espacios de trabajo conjunto (ECW) son considerados espacios creativos. Basándonos en un estudio cualitativo de los gestores y usuarios de ECW en el area de Montreal, exploramos cómo los mitos que rodean la promesa de la creatividad se enfrentan a la realidad y dan forma a las prácticas de los actores. Los resultados sugieren prácticas compensatorias diferenciadas con respecto a la brecha mito-realidad: prácticas de revalorización para los gestores y prácticas de desarrollo de un “entre-sí” para los usuarios

In Depth Exploration of the Alternative Proteome of Drosophila melanogaster.

Recent studies have shown that hundreds of small proteins were occulted when protein-coding genes were annotated. These proteins, called alternative proteins, have failed to be annotated notably due to the short length of their open reading frame (less than 100 codons) or the enforced rule establishing that messenger RNAs (mRNAs) are monocistronic. Several alternative proteins were shown to be biologically active molecules and seem to be involved in a wide range of biological functions. However, genome-wide exploration of the alternative proteome is still limited to a few species. In the present article, we describe a deep peptidomics workflow which enabled the identification of 401 alternative proteins in Drosophila melanogaster. Subcellular localization, protein domains, and short linear motifs were predicted for 235 of the alternative proteins identified and point toward specific functions of these small proteins. Several alternative proteins had approximated abundances higher than their canonical counterparts, suggesting that these alternative proteins are actually the main products of their corresponding genes. Finally, we observed 14 alternative proteins with developmentally regulated expression patterns and 10 induced upon the heat-shock treatment of embryos, demonstrating stage or stress-specific production of alternative proteins

Systems-level conservation of the proximal TCR signaling network of mice and humans

International audienceWe exploited traceable gene tagging in primary human T cells to establish the composition and dynamics of seven canonical TCR-induced protein signaling complexes (signalosomes) using affinity purification coupled with mass spectrometry (AP-MS). It unveiled how the LAT adaptor assembles higher-order molecular condensates and revealed that the proximal TCR-signaling network has a high degree of qualitative and quantitative conservation between human CD4 + and CD8 + T cells. Such systemslevel conservation also extended across human and mouse T cells and unexpectedly encompassed protein-protein interaction stoichiometry. Independently of evolutionary considerations, our study suggests that a drug targeting the proximal TCR signaling network should behave similarly when applied to human and mouse T cells. However, considering that signaling differences likely exist between the distal TCR-signaling pathway of human and mouse, our fast-track AP-MS approach should be favored to determine the mechanism of action of drugs targeting human T cell activation. An opportunity is illustrated here using an inhibitor of the LCK protein tyrosine kinase as a proof-of-concept

Connectivity mapping of glomerular proteins identifies dimethylaminoparthenolide as a new inhibitor of diabetic kidney disease

International audienceAbstract While blocking the renin angiotensin aldosterone system (RAAS) has been the main therapeutic strategy to control diabetic kidney disease (DKD) for many years, 25–30% of diabetic patients still develop the disease. In the present work we adopted a systems biology strategy to analyze glomerular protein signatures to identify drugs with potential therapeutic properties in DKD acting through a RAAS-independent mechanism. Glomeruli were isolated from wild type and type 1 diabetic (Ins2Akita) mice treated or not with the angiotensin-converting enzyme inhibitor (ACEi) ramipril. Ramipril efficiently reduced the urinary albumin/creatine ratio (ACR) of Ins2Akita mice without modifying DKD-associated renal-injuries. Large scale quantitative proteomics was used to identify the DKD-associated glomerular proteins (DKD-GPs) that were ramipril-insensitive (RI-DKD-GPs). The raw data are publicly available via ProteomeXchange with identifier PXD018728. We then applied an in silico drug repurposing approach using a pattern-matching algorithm (Connectivity Mapping) to compare the RI-DKD-GPs’s signature with a collection of thousands of transcriptional signatures of bioactive compounds. The sesquiterpene lactone parthenolide was identified as one of the top compounds predicted to reverse the RI-DKD-GPs’s signature. Oral treatment of 2 months old Ins2Akita mice with dimethylaminoparthenolide (DMAPT, a water-soluble analogue of parthenolide) for two months at 10 mg/kg/d by gavage significantly reduced urinary ACR. However, in contrast to ramipril, DMAPT also significantly reduced glomerulosclerosis and tubulointerstitial fibrosis. Using a system biology approach, we identified DMAPT, as a compound with a potential add-on value to standard-of-care ACEi-treatment in DKD

Mass spectrometry-based proteomics in clinical practice amyloid typing: state-of-the-art from a French nationwide cohort

International audienc